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Review
. 2015:2015:243868.
doi: 10.1155/2015/243868. Epub 2015 Oct 18.

The Role of TOX in the Development of Innate Lymphoid Cells

Corey R Seehus  1 , Jonathan Kaye  2
Affiliations
Review

The Role of TOX in the Development of Innate Lymphoid Cells

Corey R Seehus et al. Mediators Inflamm. 2015.

Abstract

TOX, an evolutionarily conserved member of the HMG-box family of proteins, is essential for the development of various cells of both the innate and adaptive immune system. TOX is required for the development of CD4(+) T lineage cells in the thymus, including natural killer T and T regulatory cells, as well as development of natural killer cells and fetal lymphoid tissue inducer cells, the latter required for lymph node organogenesis. Recently, we have identified a broader role for TOX in the innate immune system, demonstrating that this nuclear protein is required for generation of bone marrow progenitors that have potential to give rise to all innate lymphoid cells. Innate lymphoid cells, classified according to transcription factor expression and cytokine secretion profiles, derive from common lymphoid progenitors in the bone marrow and require Notch signals for their development. We discuss here the role of TOX in specifying CLP toward an innate lymphoid cell fate and hypothesize a possible role for TOX in regulating Notch gene targets during innate lymphoid cell development.

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Figures

Figure 1
Figure 1
Domain structure of the TOX protein. Shown in red are differences between human and mouse TOX.
Figure 2
Figure 2
Proposed model of the role of TOX in innate lymphoid cell development. We propose that IL7Rlo cells represent a CLP to CHILP transitional cell population that requires TOX for progression. Notch signaling in CLP may initiate ILC differentiation but is terminated upon downregulation of Notch at the IL7Rlo transitional stage, and TOX could influence regulation of Notch gene targets. The NK cell lineage originates from a pre-CHILP stage (EILP), possibly via the αLP progenitor that is also TOX dependent. In the absence of TOX, rNKp cells fail to develop, but a population of Lin−CD122+ cells of unknown origin or function remains. Development of tissue resident NK cells is less affected by loss of TOX than are cNK cells, possibly indicative of a distinct pathway of development. Similarly, ILC3s are found in the gut of TOX-deficient mice, but whether this is due to a TOX-independent pathway of development or homeostatic proliferation is not clear.
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References

    1. Artis D., Spits H. The biology of innate lymphoid cells. Nature. 2015;517(7534):293–301. doi: 10.1038/nature14189. - DOI - PubMed
    1. Cherrier M., Sawa S., Eberl G. Notch, Id2, and RORgammat sequentially orchestrate the fetal development of lymphoid tissue inducer cells. Journal of Experimental Medicine. 2012;209(4):729–740. doi: 10.1084/jem.20111594. - DOI - PMC - PubMed
    1. Wong S. H., Walker J. A., Jolin H. E., et al. Transcription factor RORα is critical for nuocyte development. Nature Immunology. 2012;13(3):229–236. doi: 10.1038/ni.2208. - DOI - PMC - PubMed
    1. Yang Q., Saenz S. A., Zlotoff D. A., Artis D., Bhandoola A. Cutting edge: natural helper cells derive from lymphoid progenitors. Journal of Immunology. 2011;187(11):5505–5509. doi: 10.4049/jimmunol.1102039. - DOI - PMC - PubMed
    1. Rankin L. C., Groom J. R., Chopin M., et al. The transcription factor T-bet is essential for the development of NKp46+ innate lymphocytes via the Notch pathway. Nature Immunology. 2013;14(4):389–395. doi: 10.1038/ni.2545. - DOI - PMC - PubMed

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